“During the past four weeks, have you been tired? Been exhausted? Had difficulty getting motivated to do anything at all?”

These questions — which a substantial chunk of the population probably could answer in the affirmative — appeared on a questionnaire used in a major European study published recently in the New England Journal of Medicine.

The authors were researching the effectiveness of a drug that is widely, if controversially, used to treat older adults with subclinical hypothyroidism, better known as a slightly underactive thyroid.

So many Americans take that medication — levothyroxine (brand name Synthroid, among others) — that it topped the list of prescription drugs dispensed in the United States in 2015, according to the research firm QuintilesIMS Institute.

With 121 million prescriptions annually, levothyroxine outpaced statins, blood pressure meds — and everything else. A Johns Hopkins survey published last year found that more than 15 percent of older Americans were taking it.

So you’d think these study results would come as shocking news: The European team reported that in older people with mild hypothyroidism, the drug had no significant effect on symptoms. At all.

Instead, the results bolstered what a number of geriatricians and endocrinologists have suspected for years.

“It’s a strong signal that this is an overused medication,” said Dr. Juan Brito, an endocrinologist at the Mayo Clinic. “Some people really need this medicine, but not the vast majority of people who are taking it.”

A primer: Your pituitary gland manufactures a hormone called thyrotropin, or TSH (thyroid stimulating hormone). TSH, in turn, directs the thyroid to produce hormones essential to many organs and systems: the heart, the brain, the muscles.

High blood levels of TSH indicate that the thyroid gland is less active than it should be. Usually, doctors order a blood test to measure the hormone when patients complain of symptoms suggestive of a failing thyroid — fatigue, constipation, weight gain, muscle weakness or cold sensitivity.

Often, though, doctors simply order TSH readings as part of routine blood work.

“As people get older and see doctors more often, they’re more likely to get these tests,” said Dr. Caleb Alexander, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness.

True or “overt” hypothyroidism can cause intense symptoms and, if untreated, can lead to heart disease and other threats. People with TSH readings over 10 milli-international units per liter of blood, and who have low levels of other thyroid hormones, generally get a prescription for levothyroxine — and need one.

The questions arise when TSH is only slightly higher than normal. Is that a disease?

A slightly elevated TSH may represent a normal consequence of aging. Or a temporary problem. Patients with these test results rarely develop serious hypothyroidism.

Yet millions of older Americans, diagnosed with subclinical hypothyroidism based on TSH numbers, are taking a medication that now appears pointless.

“We were very aware the practices we adopt weren’t really based on good evidence,” said Dr. David Stott, a geriatrician at the University of Glasgow who led the new study, conducted with 737 adults older than 65 in Scotland, Ireland, the Netherlands and Switzerland.

He and his colleagues found subjects (average age: 74) through laboratory databases indicating that physicians had tested their TSH at least twice. All had higher-than-normal TSH levels and, on questionnaires assessing tiredness and other hypothyroid symptoms, nearly all expressed some of the standard complaints.

Stott and his colleagues also administered a series of other tests assessing handgrip strength, speed of cognitive function, health-related quality of life, weight and blood pressure.

Then, half the group began taking levothyroxine while the others took a placebo; all were followed for at least a year. “One would expect to see a change within a year, if you were going to see a change,” Stott said.

The drug, let’s note, did what it’s designed to do: It lowered TSH to levels considered normal (in this study, 0.4 to 4.59 mIU per liter). Among placebo takers, TSH barely budged.

But, so what? On questionnaires inquiring about tiredness and other hypothyroid symptoms, on all the other pre- and post-tests, taking the drug brought no improvement.

It didn’t make patients physically stronger or mentally faster. They didn’t lose weight or feel more energetic.

“We are tending to medicalize and rush to think we need to treat it,” Stott said. But older people with a TSH under 10 mIU won’t benefit from levothyroxine, he has concluded.

Treatment of other precursor conditions, like pre-diabetes and osteopenia, has generated the same sort of criticism, it’s worth noting.

Why are so many taking levothyroxine, then? The prevalence of overt hypothyroidism hasn’t changed much, but the number of annual prescriptions keeps climbing.

Dr. David Aron, an endocrinologist at Case Western Reserve University School of Medicine, offered one explanation: Hypothyroid symptoms can be vague and nonspecific.

Tiredness, weight gain, aching muscles or joints, memory problems — how many people older than 65 don’t experience some of those?

“Are they actually due to thyroid disease or to something else?” Aron wondered. (He suggested a couple of alternative diagnoses: “Postmodern humanity. The current state of politics.”)

Thyroid function also seems simple to test for and to treat. As an explanation for common symptoms, “primary care doctors like it,” Brito said. “It’s more difficult to talk about your life or your sleep, to find out why you’re tired.”

Those doctors might also be prescribing levothyroxine based on a single TSH test. That’s a mistake, Aron said.

TSH levels vary day to day, even hour to hour, and often stabilize on their own. In fact, the new study excluded 60 percent of potential subjects because their TSH levels had returned to normal when retested, without any treatment.

Reassuringly, levothyroxine doesn’t appear to cause a lot of side effects, unless doses get too high. Compared to many drugs, the generic form isn’t expensive.

But adding one more drug becomes burdensome in itself, given the complicated, expensive medication routines many older people follow. Patients in the European study, for instance, already averaged four prescriptions.

Taking levothyroxine requires considerable juggling, too. Most patients need three or four blood tests over several months to get the dosage right.

The drug should be taken on an empty stomach. It interacts with a number of other common medications, including certain antacids. Supplements containing iron or calcium also affect its absorption.

Yet once patients begin thyroid replacement, they rarely end it, even if they feel as draggy or achy as ever. “Here’s a golden opportunity for many patients to simplify their medication regimens,” Alexander said.

Before starting it, consider Aron’s approach. When older people come in with mild symptoms that might be thyroid-related — or might not — he tests for TSH more than once.

If it remains slightly elevated, “we can follow this and see how it goes,” he tells patients. “Alternatively, we could try a course of medication for a couple of months.”

“If it helps you feel better, great. If it doesn’t, we stop.”